This proposal is designed to define the biochemical mechanisms through which hormones and other physiologically active compounds interact to regulate smooth muscle contractility in the uterus. This tissue is an excellent model for the examination of the physiological and molecular mechanisms of hormonal interaction in target organs in general. In physiological studies, control of alpha and beta adrenergic catecholamine receptor concentration in relation to contractile state, catecholamine and reproductive steroid (estrogen and progesterone) concentrations will be assessed in pregnant, cycling, castrate and sex steroid treated castrate rats. The mechanism through which the reproductive steroids regulate the membrane density of myometrial catecholamine receptors will be investigated by comparing the effects of estrogen on smooth muscle cell membrane synthesis and synthesis of the beta-adrenergic receptor using purified receptor. The biochemical consequences of sex steroid hormone modulation of cell membrane receptors will be determined by evaluating their effects on beta-adrenergic catecholamine-sensitive adenylate cyclase as well as other components of the myometrial adneylate cylase system, particularly cAMP-dependent protein kinase and its phosphoprotein substrates. The role of these substrates in the regulation of contractility is to be defined, particularly with respect to membrane Ca ions-transport activity and alteration of membrane catecholamine receptor properties. Through these investigations, we intend to clarity the mechanisms by which cells adjust to regulate their responses to circulating stimuli in order to maintain an optiaml homeostatic state.